Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions.

CONTEXT: Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult. OBJECTIVE: The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions. DESIGNS AND METHODS: We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology. RESULTS: Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)). CONCLUSION: We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin.

Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma.

Intravascular large B-cell lymphoma is a rare entity characterized by the proliferation of neoplastic lymphocytes in the lumen of small blood vessels and high mortality. Diagnosis of intravascular lymphoma is often delayed or established postmortem. Here, we report the case of a 48-year-old woman presenting hemophagocytic syndrome, with pituitary gland and neurological involvement. Diagnosis of intravascular large B-cell lymphoma was made on perisplenic vessels, while liver and bone marrow biopsy was noncontributive. This case demonstrates the importance of thorough histopathologic investigations in the setting of high suspicion.

T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly.

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.

Acute aseptic meningitis as the initial presentation of a macroprolactinoma.

BACKGROUND: Meningitis is an uncommon complication of an untreated pituitary macroadenoma. Meningitis may occur in patients with macroadenomas who have undergone transsphenoidal surgery and radiotherapy and is usually associated with rhinorrhea. Less commonly, cerebrospinal fluid rhinorrhea has been reported as a complication of treatment of prolactinomas by dopamine agonists. Cerebrospinal fluid rhinorrhea in cases of untreated pituitary macroadenoma is reported only in isolated cases. Acute bacterial meningitis without rhinorrhea in patients with an untreated pituitary macroadenoma is an exceptional finding with only three previously reported cases. CASE PRESENTATION: A 31-year-old male was urgently admitted for headache, fever and visual loss. Neuroimaging disclosed an invasive pituitary lesion. Cerebrospinal fluid leakage was not clinically detected. Lumbar puncture showed acute meningitis. Blood tests revealed increased inflammatory markers, a serum prolactin of 9000 ng/ml (2.5-11 ng/ml) and panhypopituitarism. Intravenous antibiotics and hydrocortisone replacement therapy were initiated, leading to a favorable clinical outcome. An endoscopic transsphenoidal debulking procedure was performed, it showed that the sphenoid floor was destroyed and the sinus occluded by a massive tumor. CONCLUSIONS: Meningitis should be ruled out in patients with a pituitary mass who present with headache and increased inflammatory tests, even in the absence of rhinorrhea.

Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients.

CONTEXT: Prolactinoma is the most frequent pituitary tumour among women of child-bearing age. Only a few studies have addressed the outcome of prolactinoma after pregnancy. OBJECTIVE: To study remission, defined as prolactin normalization without medical treatment, after pregnancy and lactation in women with prolactinoma. PATIENTS AND METHODS: A retrospective study conducted in 2 Belgian academic centres including 73 patients (54 microprolactinomas and 19 macroprolactinomas) with 104 pregnancies continuing beyond first trimester. Dopamine agonists were stopped in early pregnancy in all treated cases. Prolactin level and adenoma size at pituitary magnetic resonance imaging (MRI) were recorded before pregnancy and throughout follow-up. RESULTS: Thirty of 73 women (41%) were in remission after a median follow-up of 22 months after delivery or cessation of lactation. Adenoma size at diagnosis was smaller in women in remission (5 vs 8 mm). There was a nonsignificant higher rate of remission for microprolactinomas than for macroprolactinoma (46% vs 26%). The first pituitary MRI after pregnancy and lactation showed no tumour and a decreased adenoma size in 23% and 39% of women, respectively. MRI normalization was associated with remission. The number of pregnancies per woman as well as breastfeeding and its duration did not influence remission rate. CONCLUSION: More than 40% of women with previous diagnosis of prolactinoma have normal PRL level without medical treatment for a median follow-up of 22 months after pregnancy and lactation. The likelihood of remission is associated with a smaller initial adenoma size and normalization of pituitary MRI after pregnancy.

Giant prolactinomas in women.

OBJECTIVE: To characterise distinctive clinical features of giant prolactinomas in women. DESIGN: A multicentre, retrospective case series and literature review. METHODS: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 µg/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. RESULTS: The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female:male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P<0.05). All cases diagnosed before the age of 15 years were boys. In women (n=34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10,000 µg/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (<2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. CONCLUSION: Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.

Accurate pre-operative localization of pathological parathyroid glands using 11C-methionine PET/CT.

OBJECTIVE: The pre-operative technique most routinely used to localize pathological parathyroid glands (PPG), prior to minimal access surgery (MAS), relies on 99mTc-sestamibi (MIBI) scintigraphy. Positron emission tomography (PET) using the radiolabelled amino acid 11C-methionine as the tracer agent offers a technological alternative to localize PPG. In this study we evaluated the sensitivity of 11C-methionine PET/CT (MET-PET/CT) for PPG detection and the extent to which MET-PET/CT images may contribute to the planning of surgical procedures. DESIGN: Thirty patients were included, 22 with primary hyperparathyroidism and eight with secondary hyperparathyroidism. Patients suspected of suffering from parathyroid hyperplasia underwent a complete surgical exploration of the neck region. In those suspected of parathyroid adenoma, surgery was limited to the presumed localization described by MET-PET/CT. To specifically address the additional benefit of the MET-PET/CT in terms of surgical planning and procedure, the surgeon classified the patients into two categories depending on the type of benefit, or the reason for the absence of benefit, occurring in each case. We also compared the sensitivity of MET-PET/CT and MIBI scintigraphy. RESULTS: The total number of lesions removed was 46 (24 adenomatous and 22 hyperplastic). Globally, MET-PET/CT provided additional benefit to surgery in 15 out of 30 cases (50%). The sensitivity of 11C-methionine PET/CT and MIBI scintigraphy was respectively 92% and 95% for adenoma, and 68% and 59% for hyperplasia, on the basis of available resected lesions. CONCLUSION: MET-PET/CT appears a reliable technique to guide MAS of parathyroid glands.